Citation: Yingli Zhu, Jie Qian, Kunqian Yu, Jing Hou, Yeshuo Ma, Fei Chen, Jie Dong, Wenbin Zeng. Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods[J]. Chinese Chemical Letters, ;2024, 35(2): 108948. doi: 10.1016/j.cclet.2023.108948 shu

Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

Yingli Zhu ^a ,
Jie Qian ^b ,
Kunqian Yu ^c ,
Jing Hou ^a ,
Yeshuo Ma ^d ,
Fei Chen ^a ,
Jie Dong ^{a, *,} ,
Wenbin Zeng ^{a, *,}

a.
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China
b.
National Engineering Research Center of Rice and Byproduct Deep Processing, School of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
c.
State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
d.
Department of Geriatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China

jiedong@csu.edu.cn

wbzeng@hotmail.com

Received Date: 11 July 2023
Revised Date: 17 August 2023
Accepted Date: 18 August 2023
Available Online: 19 August 2023

Figures(4)

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development, disease diagnosis, and basic theoretical research. Aminopeptidase N (APN), as a representative tumor biomarker with anti-tumor potential, still lacks a high-precision theranostic probe specifically targeting it. In this study, a novel quaternity design strategy for APN theranostic probe was developed. This proposed strategy utilizes advanced machine learning and molecular dynamics simulations, and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional fragments. Through this strategy, a unique "Off–On" theranostic probe, ABTP-DPTB, was ingeniously constructed to light up APN through fluorescence restoration, relying on conformation-induced effects and solvent restriction. Differ from the common diagnostic probes, the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ imaging. The fabricated probe was used for detecting and inhibiting APN in various environments, with a better in vitro inhibitory than golden-standard drug bestatin.
- Theranostic probe,
- Artificial intelligence,
- Conformational restriction,
- Fluorescence restoration,
- Design strategy
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